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参与急性早幼粒细胞白血病细胞增殖的miR-125b靶标的鉴定。

Identification of miR-125b targets involved in acute promyelocytic leukemia cell proliferation.

作者信息

Zhang Yikai, Zeng Chengwu, Lu Shuai, Qin Tianyu, Yang Lijian, Chen Shaohua, Chen Jie, Li Yangqiu

机构信息

Institute of Hematology, Medical College, Jinan University, Guangzhou, 510632, China; Key Laboratory for Regenerative Medicine of Ministry of Education, Jinan University, Guangzhou, 510632, China; First Affiliated Hospital, Jinan University, Guangzhou 510632, China.

Institute of Hematology, Medical College, Jinan University, Guangzhou, 510632, China; Key Laboratory for Regenerative Medicine of Ministry of Education, Jinan University, Guangzhou, 510632, China; First Affiliated Hospital, Jinan University, Guangzhou 510632, China.

出版信息

Biochem Biophys Res Commun. 2016 Sep 30;478(4):1758-63. doi: 10.1016/j.bbrc.2016.09.020. Epub 2016 Sep 6.

Abstract

Acute promyelocytic leukemia (APL) is characterized by the presence of the PML-RARα fusion protein. We have previously found that PML-RARα-regulated miR-125b is highly expressed in APL; however, the characteristics of the regulatory effects and mechanisms of miR-125b involved in APL proliferation have yet to be clarified. In this study, we demonstrate that miR-125b promotes the proliferation of APL cells with the involvement of the PI3K/Akt and MAPK signaling pathways. Furthermore, we identified BTG2, MAP3K11, RPS6KA1 and PRDM1 as putative targets of miR-125b, which we verified using luciferase reporter constructs. Moreover, we demonstrate that the expression of miR-125b targets is downregulated in leukemic cells in patients with APL. Thus, our results provide evidence that miR-125b can modulate multiple oncogenic cell proliferation pathways and may be a novel therapeutic target for APL.

摘要

急性早幼粒细胞白血病(APL)的特征是存在PML-RARα融合蛋白。我们之前发现,PML-RARα调控的miR-125b在APL中高表达;然而,miR-125b参与APL增殖的调控作用及机制的特点尚未阐明。在本研究中,我们证明miR-125b通过PI3K/Akt和MAPK信号通路促进APL细胞的增殖。此外,我们鉴定出BTG2、MAP3K11、RPS6KA1和PRDM1为miR-125b的假定靶标,并使用荧光素酶报告基因构建体进行了验证。此外,我们证明APL患者白血病细胞中miR-125b靶标的表达下调。因此,我们的结果提供了证据,表明miR-125b可调节多种致癌细胞增殖途径,可能是APL的一个新的治疗靶点。

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